Publications by authors named "Renzhi Wang"

273 Publications

Validation of perihematomal edema expansion as a new imaging biomarker to predict clinical outcome in patients with intracerebral hemorrhage.

J Stroke Cerebrovasc Dis 2022 Aug 3;31(9):106692. Epub 2022 Aug 3.

Department of Neurosurgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China. Electronic address:

Objectives: The use of hematoma expansion (HE) in intracerebral hemorrhage (ICH) patients is limited due to its low sensitivity. Perihematomal edema (PHE) has been considered an important marker of secondary brain injury after ICH. Enrolling PHE expansion to redefine traditional ICH expansion merits exploration.

Materials And Methods: This study analyzed a cohort of patients with spontaneous ICH. The hematoma and PHE were manually segmented. Logistic regression analysis was utilized to identify risk factors for poor outcomes. Receiver operating characteristic curve analysis was performed to calculate the predictive values of PHE expansion and HE. Poor neurological outcome was defined as a modified Rankin Scale score of 4-6 at 90 days.

Results: Overall, 223 target patients were enrolled in the study. Multivariable analysis showed the larger PHE expansion is the independent risk factors for poor prognosis. The predictive value of absolute PHE expansion (AUC=0.776, sensitivity=67.9%, specificity=77.0%) was higher than that of absolute HE (AUC=0.573, sensitivity=41.7%, specificity=87.1%) and HE (>6 ml) (AUC=0.594, sensitivity=23.8%, specificity=95.0%). The best cutoff for early absolute/relative PHE expansion resulting in a poor outcome was 5.96 ml and 31%.

Conclusions: Early PHE expansion was associated with a poor outcome, characterized by a better predictive value than HE.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2022.106692DOI Listing
August 2022

A Convolutional Neural Network Model for Detecting Sellar Floor Destruction of Pituitary Adenoma on Magnetic Resonance Imaging Scans.

Front Neurosci 2022 4;16:900519. Epub 2022 Jul 4.

Department of Neurosurgery, Dongfang Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.

Objective: Convolutional neural network (CNN) is designed for image classification and recognition with a multi-layer neural network. This study aimed to accurately assess sellar floor invasion (SFI) of pituitary adenoma (PA) using CNN.

Methods: A total of 1413 coronal and sagittal magnetic resonance images were collected from 695 patients with PAs. The enrolled images were divided into the invasive group ( = 530) and the non-invasive group ( = 883) according to the surgical observation of SFI. Before model training, 100 images were randomly selected for the external testing set. The remaining 1313 cases were randomly divided into the training and validation sets at a ratio of 80:20 for model training. Finally, the testing set was imported to evaluate the model performance.

Results: A CNN model with a 10-layer structure (6-layer convolution and 4-layer fully connected neural network) was constructed. After 1000 epoch of training, the model achieved high accuracy in identifying SFI (97.0 and 94.6% in the training and testing sets, respectively). The testing set presented excellent performance, with a model prediction accuracy of 96%, a sensitivity of 0.964, a specificity of 0.958, and an area under the receptor operator curve (AUC-ROC) value of 0.98. Four images in the testing set were misdiagnosed. Three images were misread with SFI (one with conchal type sphenoid sinus), and one image with a relatively intact sellar floor was not identified with SFI.

Conclusion: This study highlights the potential of the CNN model for the efficient assessment of PA invasion.
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http://dx.doi.org/10.3389/fnins.2022.900519DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9289618PMC
July 2022

3D Shuffle-Mixer: An Efficient Context-Aware Vision Learner of Transformer-MLP Paradigm for Dense Prediction in Medical Volume.

IEEE Trans Med Imaging 2022 Jul 18;PP. Epub 2022 Jul 18.

Dense prediction in medical volume provides enriched guidance for clinical analysis. CNN backbones have met bottleneck due to lack of long-range dependencies and global context modeling power. Recent works proposed to combine vision transformer with CNN, due to its strong global capture ability and learning capability. However, most works are limited to simply applying pure transformer with several fatal flaws (i.e., lack of inductive bias, heavy computation and little consideration for 3D data). Therefore, designing an elegant and efficient vision transformer learner for dense prediction in medical volume is promising and challenging. In this paper, we propose a novel 3D Shuffle-Mixer network of a new Local Vision Transformer-MLP paradigm for medical dense prediction. In our network, a local vision transformer block is utilized to shuffle and learn spatial context from full-view slices of rearranged volume, a residual axial-MLP is designed to mix and capture remaining volume context in a slice-aware manner, and a MLP view aggregator is employed to project the learned full-view rich context to the volume feature in a view-aware manner. Moreover, an Adaptive Scaled Enhanced Shortcut is proposed for local vision transformer to enhance feature along spatial and channel dimensions adaptively, and a CrossMerge is proposed to skip-connect the multi-scale feature appropriately in the pyramid architecture. Extensive experiments demonstrate the proposed model outperforms other state-of-the-art medical dense prediction methods.
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http://dx.doi.org/10.1109/TMI.2022.3191974DOI Listing
July 2022

Defining Delayed Perihematomal Edema Expansion in Intracerebral Hemorrhage: Segmentation, Time Course, Risk Factors and Clinical Outcome.

Front Immunol 2022 9;13:911207. Epub 2022 May 9.

Department of Neurosurgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.

We attempt to generate a definition of delayed perihematomal edema expansion (DPE) and analyze its time course, risk factors, and clinical outcomes. A multi-cohort data was derived from the Chinese Intracranial Hemorrhage Image Database (CICHID). A non-contrast computed tomography (NCCT) -based deep learning model was constructed for fully automated segmentation hematoma and perihematomal edema (PHE). Time course of hematoma and PHE evolution correlated to initial hematoma volume was volumetrically assessed. Predictive values for DPE were calculated through receiver operating characteristic curve analysis and were tested in an independent cohort. Logistic regression analysis was utilized to identify risk factors for DPE formation and poor outcomes. The test cohort's Dice scores of lesion segmentation were 0.877 and 0.642 for hematoma and PHE, respectively. Overall, 1201 patients were enrolled for time-course analysis of ICH evolution. A total of 312 patients were further selected for DPE analysis. Time course analysis showed the growth peak of PHE approximately concentrates in 14 days after onset. The best cutoff for DPE to predict poor outcome was 3.34 mL of absolute PHE expansion from 4-7 days to 8-14 days (AUC=0.784, sensitivity=72.2%, specificity=81.2%), and 3.78 mL of absolute PHE expansion from 8-14 days to 15-21 days (AUC=0.682, sensitivity=59.3%, specificity=92.1%) in the derivation sample. Patients with DPE was associated with worse outcome (OR: 12.340, 95%CI: 6.378-23.873, P<0.01), and the larger initial hematoma volume (OR: 1.021, 95%CI: 1.000-1.043, P=0.049) was the significant risk factor for DPE formation. This study constructed a well-performance deep learning model for automatic segmentations of hematoma and PHE. A new definition of DPE was generated and is confirmed to be related to poor outcomes in ICH. Patients with larger initial hematoma volume have a higher risk of developing DPE formation.
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http://dx.doi.org/10.3389/fimmu.2022.911207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9125313PMC
May 2022

Application of Convolutional Neural Network in the Diagnosis of Cavernous Sinus Invasion in Pituitary Adenoma.

Front Oncol 2022 14;12:835047. Epub 2022 Apr 14.

Department of Neurosurgery, The Fuzong Clinical Medical College of Fujian Medical University, Fuzhou, China.

Objectives: Convolutional neural network (CNN) is a deep-learning method for image classification and recognition based on a multi-layer NN. In this study, CNN was used to accurately assess cavernous sinus invasion (CSI) in pituitary adenoma (PA).

Methods: A total of 371 patients with PA were enrolled in the retrospective study. The cohort was divided into the invasive ( = 102) and non-invasive groups ( = 269) based on surgically confirmed CSI. Images were selected on the T1-enhanced imaging on MR scans. The cohort underwent a fivefold division of randomized datasets for cross-validation. Then, a tenfold augmented dataset (horizontal flip and rotation) of the training set was enrolled in the pre-trained Resnet50 model for transfer learning. The testing set was imported into the trained model for evaluation. Gradient-weighted class activation mapping (Grad-CAM) was used to obtain the occlusion map. The diagnostic values were compared with different dichotomizations of the Knosp grading system (grades 0-1/2-4, 0-2/3a-4, and 0-3a/3b-4).

Results: Based on Knosp grades, 20 cases of grade 0, 107 cases of grade 1, 82 cases of grade 2, 104 cases of grade 3a, 22 cases of grade 3b, and 36 cases of grade 4 were recorded. The CSI rates were 0%, 3.7%, 18.3%, 37.5%, 54.5%, and 88.9%. The predicted accuracies of the three dichotomies were 60%, 74%, and 81%. The area under the receiver operating characteristic (AUC-ROC) of Knosp grade for CSI prediction was 0.84; the cutoff was 2.5 with a Youden value of 0.62. The accuracies of the CNN model ranged from 0.80 to 0.96, with AUC-ROC values ranging from 0.89 to 0.98. The Grad-CAM saliency maps confirmed that the region of interest of the model was around the sellar region.

Conclusions: We constructed a CNN model with a high proficiency at CSI diagnosis. A more accurate CSI identification was achieved with the constructed CNN than the Knosp grading system.
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http://dx.doi.org/10.3389/fonc.2022.835047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9047893PMC
April 2022

Surgical Outcomes of Clival Chordoma Through Endoscopic Endonasal Approach: A Single-Center Experience.

Front Endocrinol (Lausanne) 2022 6;13:800923. Epub 2022 Apr 6.

Department of Neurosurgery, Xuanwu Hospital Capital Medical University, Beijing, China.

Objective: Clival chordoma is a locally aggressive tumor with low metastatic potential. In the past decade, endoscopic endonasal approach (EEA) for clival chordoma has had a higher resection rate and a lower morbidity rate than transcranial approaches. Here, we present our initial single-center experience after EEA of clival chordomas.

Patients And Methods: This study retrospectively analyzed 17 consecutive patients with clival chordoma who received EEA in our department between March 2015 and September 2021. The operation was performed by a single surgeon with EEA. The clinical and pathological characteristics were analyzed along with the surgical outcomes and complications.

Results: A total of 17 consecutive patients with clival chordoma received EEA with a median follow-up of 29.2 months (range 1-79). Gross total resection (GTR) was performed in 7 cases (41%), subtotal resection (STR) in 7 case (41%) and partially resection (PR) in 3 cases (18%). Cerebrospinal fluid leakage occurred in 2 cases (12%) and meningitis developed in 3 patients (18%) which were all successfully treated with intravenous antibiotics without any complications. There were no perioperative deaths or new focal neurological deficits postoperatively. Four in 7 patients with STR have had radiotherapy while the other three chose to be monitored. Till the last follow-up, three patients in STR group who received radiotherapy (3 in 4) had no tumor regrowth, while one in STR group with radiotherapy (1 in 4) showed tumor progression. Two patients in STR group without radiotherapy (2 in 3) showed stable tumor while the left one (1 in 3) showed tumor progression. One patient in the PR group died of tumor progression 2 years postoperation and the other one showed tumor progression and died of lung cancer 1 year postoperation. In addition, 1 in 7 patients with GTR had tumor recurrence after 10 months and developed surgical pathway seeding in the spinal canal in C1 after 16 months. No recurrence occurred in the other 6 cases with GTR during the follow-up.

Conclusion: Although more cases are needed, our case series showed EEA is a safe and reliable method for clival chordoma with high resection rates and low morbidity rates. GTR without tumor residuum would improve the outcome.
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http://dx.doi.org/10.3389/fendo.2022.800923DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9019489PMC
April 2022

Multi-Omics Investigations Revealed Underlying Molecular Mechanisms Associated With Tumor Stiffness and Identified Sunitinib as a Potential Therapy for Reducing Stiffness in Pituitary Adenomas.

Front Cell Dev Biol 2022 15;10:820562. Epub 2022 Mar 15.

Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Pituitary adenomas (PAs) are the second most common intracranial neoplasms. Total surgical resection was extremely important for curing PAs, whereas tumor stiffness has gradually become the most critical factor affecting the resection rate in PAs. We aimed to investigate the molecular mechanisms of tumor stiffening and explore novel medications to reduce stiffness for improving surgical remission rates in PA patients. RNA sequencing, whole-genome bisulfite sequencing, and whole exome sequencing were applied to identify transcriptomic, epigenomic, and genomic underpinnings among 11 soft and 11 stiff PA samples surgically resected from patients at Peking Union Medical College Hospital (PUMCH). GH3 cell line and xenograft PA model was used to demonstrate therapeutic effect of sunitinib, and atomic force microscopy (AFM) was used to detect the stiffness of tumors. Tumor microenvironment analyses and immunofluorescence staining indicated endothelial cells (ECs) and cancer-associated fibroblasts (CAFs) were more abundant in stiff PAs. Weighted gene coexpression network analysis identified the most critical stiffness-related gene (SRG) module, which was highly correlated with stiff phenotype, ECs and CAFs. Functional annotations suggested SRGs might regulate PA stiffness by regulating the development, differentiation, and apoptosis of ECs and CAFs and related molecular pathways. Aberrant DNA methylation and m6A RNA modifications were investigated to play crucial roles in regulating PA stiffness. Somatic mutation analysis revealed increased intratumoral heterogeneity and decreased response to immunotherapy in stiff tumors. Connectivity Map analysis of SRGs and pRRophetic algorithm based on drug sensitivity data of cancer cell lines finally determine sunitinib as a promising agent targeting stiff tumors. Sunitinib inhibited PA growth and , and also reduced tumor stiffness in xenograft PA models detected by AFM. This is the first study investigating the underlying mechanisms contributing to the stiffening of PAs, and providing novel insights into medication therapy for stiff PAs.
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http://dx.doi.org/10.3389/fcell.2022.820562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8965615PMC
March 2022

The Clinical and Pathological Characteristics of Refractory Pituitary Adenomas: A Single Center Experience.

Front Oncol 2022 16;12:846614. Epub 2022 Mar 16.

Chinese Pituitary Specialists Congress, Beijing, China.

Background: Most of pituitary adenomas (PAs) are slow-growing benign tumors which can be cured or controlled by conventional therapies, including surgery, medical treatment or radiotherapy. A small set of PAs, usually known as aggressive PAs or refractory PAs, present with more aggressive behavior and lead to poorer prognosis than classical PAs.

Methods: We retrospectively analyzed the clinical and pathological characteristics of 44 patients who were diagnosed with refractory PAs by a multidisciplinary team (MDT). All the patients' demographic characteristics, radiological findings, Knosp grade, treatment details and clinical outcomes were abstracted from the medical records. Additionally, 44 patients with nonrefractory PAs (NRPAs) matched for age and gender were selected to serve as the control group.

Results: Despite using all combined treatments including surgery, radiotherapy and conventional medical treatments, all the refractory PAs showed tumor progression or hormone hypersecretion which caused increased morbidity and mortality and remained challenging to management. Compared with those of the non-refractory PAs, the tumor size, invasive rate and tumor growth rate (TGR) were significantly higher in the refractory PAs. TGR >2.2% per month may be considered as a preoperative indicator of refractoriness. The Ki-67 index in the refractory PAs were all ≥3%. EGFR, but not MMP2 or MMP9, was significantly overexpressed in refractory PAs compared with the corresponding levels in nonrefractory PAs.

Conclusion: Refractory PAs are unresponsive to surgery, radiotherapy and conventional medical treatments with a poor prognosis. Moreover, a TGR ≥2.2% per month, Ki-67 index ≥3% and EGFR overexpression may be independent predictors of clinical refractoriness.
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http://dx.doi.org/10.3389/fonc.2022.846614DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8966407PMC
March 2022

Editorial: Refractory Pituitary Adenoma-Current Challenges and Emerging Treatments.

Front Endocrinol (Lausanne) 2022 9;13:868174. Epub 2022 Mar 9.

Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, CA, United States.

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http://dx.doi.org/10.3389/fendo.2022.868174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8959341PMC
April 2022

Automatic Brain Midline Surface Delineation on 3D CT Images with Intracranial Hemorrhage.

IEEE Trans Med Imaging 2022 Mar 17;PP. Epub 2022 Mar 17.

Brain midline delineation plays an important role in guiding intracranial hemorrhage surgery, which still remains a challenging task since hemorrhage shifts the normal brain configuration. Most previous studies detected brain midline on 2D plane and did not handle hemorrhage cases well. We propose a novel and efficient hemisphere-segmentation framework (HSF) for 3D brain midline surface delineation. Specifically, we formulate the brain midline delineation as a 3D hemisphere segmentation task, and employ an edge detector and a smooth regularization loss to generate the midline surface. We also introduce a distance-weighted map to keep the attention on the midline. Furthermore, we adopt rectification learning to handle various head poses. Finally, considering the complex situation of ventricle break-in for hemorrhages in bilateral intraventricular (B-IVH) cases, we identify those cases via a classification model and design a midline correction strategy to locally adjust the midline. To our best knowledge, it is the first study focusing on delineating the brain midline surface on 3D CT images of hemorrhage patients and handling the situation of ventricle break-in. Extensive validation on our large in-house datasets (519 patients) and the public CQ500 dataset (491 patients), demonstrates that our method outperforms state-of-the-art methods on brain midline delineation.
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http://dx.doi.org/10.1109/TMI.2022.3160184DOI Listing
March 2022

Transsphenoidal Surgery of Corticotroph Adenomas With Cavernous Sinus Invasion: Results in a Series of 86 Consecutive Patients.

Front Oncol 2022 8;12:810234. Epub 2022 Feb 8.

Department of Neurosurgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China.

Objective: Transsphenoidal surgery (TSS) is the first-line treatment for corticotroph adenomas. Although most corticotroph adenomas are noninvasive microadenomas, a small subset of them invading cavernous sinus (CS) is notoriously difficult to manage. The aim of this study was to evaluate the surgical outcome of corticotroph adenomas with CSI from a single center.

Patients And Methods: The clinical features and outcomes of CD patients who underwent TSS between January 2000 and September 2019 at Peking Union Medical College Hospital were collected from medical records. The clinical, endocrinological, radiological, histopathological, and surgical outcomes, and a minimum 12-month follow-up of patients with corticotroph adenomas invading CS were retrospectively reviewed.

Results: Eighty-six patients with corticotroph adenomas invading CS were included in the study. The average age at TSS was 37.7 years (range, 12 to 67 years), with a female-to-male ratio of 3.1:1 (65/21). The median duration of symptoms was 52.6 months (range, 1.0 to 264 months). The average of maximum diameter of tumor was 17.6 mm (range, 4.5-70 mm). All included 86 patients underwent TSS using a microscopic or an endoscopic approach. Gross total resection was achieved in 63 patients (73.3%), subtotal resection was attained in 18 (20.9%), and partial resection was achieved in 5 (5.8%). After surgery, the overall postoperative immediate remission rate was 48.8% (42/86); 51.2% (44/86) of patients maintained persistent hypercortisolism. In 42 patients with initial remission, 16.7% (7/42) experienced a recurrence. In these patients with persistent disease and recurrent CD, data about further treatment were available for 30 patients. Radiotherapy was used for 15 patients, and 4 (26.7%) of them achieved biochemical remission. Repeat TSS was performed in 5 patients, and none achieved remission. Medication was administered in 4 patients, and one of them obtained disease control. Adrenalectomy was performed in 6 patients, and 5 (83.3%) achieved biochemical remission. At the last follow-up, 10 of 30 patients (33.3%) were in remission, and 20 patients still had persistent disease.The remission rate in corticotroph adenomas with cavernous sinus invasion (CSI) that underwent gross total resection and first TSS was significantly higher than that in patients undergoing subtotal resection, partial resection, and a second TSS (all p < 0.05). However, there was no significant difference in the remission rate between patients with different tumor sizes, Knosp grades, and surgical approaches (p > 0.05).

Conclusion: The management of corticotroph adenomas with CSI remain a therapeutic challenge due to incomplete resection of invasive and/or a large adenoma. With the application of multiple techniques, approximately half of the patients could achieve gross total resection and biochemical remission TSS by experienced neurosurgeons. The extent of tumor resection and the number of operations were associated with surgical remission rate in corticotroph adenomas with CSI. If the remission was not achieved by surgery, other treatments including radiotherapy, medical therapy, and even bilateral adrenalectomy are required.
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http://dx.doi.org/10.3389/fonc.2022.810234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8861297PMC
February 2022

Determinants of immediate and long-term remission after initial transsphenoidal surgery for acromegaly and outcome patterns during follow-up: a longitudinal study on 659 patients.

J Neurosurg 2022 Jan 14:1-11. Epub 2022 Jan 14.

1Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing.

Objective: Treatment outcomes following initial transsphenoidal surgery (TSS) for acromegaly are erratic. Identifying outcome patterns can assist in informing patients about possible treatment outcomes and planning for individualized adjuvant treatments in advance. In this study, the authors aimed to investigate the immediate and long-term endocrine remission rates following initial TSS for acromegaly, identify clinical determinants of treatment outcomes, and explore outcome patterns during a long-term follow-up and the pattern-specific patient features.

Methods: This prospective, single-center, longitudinal cohort study enrolled patients with acromegaly who underwent TSS in the period from 2015 to 2018 at the authors' institution. Immediate remission, assessed on the 2nd postoperative morning, and long-term remission, assessed at least 18 months after TSS, were evaluated according to the strict 2010 consensus criteria (random growth hormone [GH] < 1 ng/ml or GH nadir < 0.4 ng/ml after oral glucose tolerance test, and age- and sex-normalized insulin-like growth factor 1). Univariate and bivariate regression analyses were used to identify determinants of remission.

Results: A total of 659 patients with acromegaly (average age 42 years, 44% males) underwent TSS for pituitary adenomas (macroadenomas, 85%; invasive tumors, 35%) and were followed up during a median of 51 months. Immediate and long-term remission rates after initial TSS were 37% and 69%, respectively. Older age at diagnosis (OR 1.7), male sex (OR 1.6), smaller tumors (OR 2.0), noninvasive tumors (OR 4.8), and tumors positive for follicle-stimulating hormone/luteinizing hormone (OR 1.5) were predictors of immediate surgical remission. In addition to the above predictors, lower preoperative GH (OR 2.4), absence of preoperative central hypothyroidism (OR 2.6), and endoscopic TSS (OR 10.6) were predictors of long-term remission. Regression analyses revealed that endoscopic TSS (OR 2.8, 95% CI 1.524-5.291, p = 0.001), absence of cavernous sinus invasion (OR 4.1, 95% CI 2.522-6.613, p < 0.001), older age (OR 1.03, 95% CI 1.006-1.048, p = 0.013), and male sex (OR 2.0, 95% CI 1.224-3.247, p = 0.006) were independent determinants of long-term remission. Five outcome patterns were identified based on the changes in hormonal results during follow-up, including continuous remission (34%), refractory acromegaly (28%), delayed remission (21%), remission after adjuvant therapy (14%), and recurrence after initial remission (3%). The clinical characteristics of each subgroup were identified.

Conclusions: Cavernous sinus invasion, age at diagnosis, and sex are the best determinants of immediate and long-term remission after initial TSS for acromegaly. Endoscopic TSS predicts a higher long-term remission rate than that with microscopic TSS. The authors identified five outcome patterns in acromegaly and group-specific patient characteristics for clinical decision-making.
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http://dx.doi.org/10.3171/2021.11.JNS212137DOI Listing
January 2022

Hyperprolactinemia and Hypopituitarism in Acromegaly and Effect of Pituitary Surgery: Long-Term Follow-up on 529 Patients.

Front Endocrinol (Lausanne) 2021 26;12:807054. Epub 2022 Jan 26.

Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Purpose: Studies on hyperprolactinemia and hypopituitarism in acromegaly are limited. We aimed to analyze the preoperative status, postoperative alterations, and correlated factors of hyperprolactinemia and hypopituitarism in acromegaly patients.

Methods: This is a single-center cohort study with long-term follow-up. We prospectively enrolled 529 acromegaly patients. Hyperprolactinemia and hypopituitarism were evaluated by testing hypothalamus-pituitary-end organ (HPEO) axes hormones before and after surgery.

Results: Hyperprolactinemia (39.1%) and hypopituitarism (34.8%) were common in acromegaly. The incidences of axis-specific hypopituitarism varied (hypogonadism, 29.7%; hypothyroidism, 5.9%; adrenal insufficiency, 5.1%), and multiple HPEO axes dysfunction was diagnosed in 5.3% of patients. Patients with preoperative hyperprolactinemia [hazard ratio (HR)=1.39 (1.08-1.79); =0.012], hypogonadism [HR=1.32 (1.01-1.73); =0.047], and hypothyroidism [HR=3.49 (1.90-6.44); <0.001] had higher recurrence rates than those without. Age, sex, body mass index, tumor size, invasiveness, prolactin staining, ki-67 index, and GH/IGF-1 levels were significantly correlated with preoperative hypopituitarism and hyperprolactinemia. At median 34-month follow-up after surgery, hyperprolactinemia in 95% and axis-specific hypopituitarism in 54%-71% of patients recovered, whereas new-onset hypopituitarism (hypogonadism, 6.2%; hypothyroidism, 4.0%; adrenal insufficiency, 3.2%) was also diagnosed. A shorter tumor diameter was associated with the normalization of preoperative hyperprolactinemia after surgery. Cavernous sinus non-invasion, a shorter tumor diameter, cure at follow-up, and a lower GH nadir level were associated with the improvement of preoperative hypopituitarism after surgery. A larger tumor diameter was associated with the newly developed hypopituitarism after surgery.

Conclusion: Hyperprolactinemia and hypopituitarism are common among acromegaly patients and predict worse surgical outcomes. After surgery, improvement and worsening of HPEO axes function co-exist. Correlated factors are identified for clinical management.
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http://dx.doi.org/10.3389/fendo.2021.807054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8825499PMC
March 2022

Functioning gonadotroph adenomas in premenopausal women: clinical and molecular characterization and review of the literature.

Pituitary 2022 Jun 9;25(3):454-467. Epub 2022 Feb 9.

Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, 1# Shuai Fu Yuan, Dong Dan, Beijing, 100730, China.

Purpose: To summary the clinical features of premenopausal women with functioning gonadotroph adenomas (FGAs) and preliminarily explore their molecular characterization.

Methods: 12 premenopausal females with FGAs in our center were retrospectively analyzed. Previously reported cases were also summarized. The patients were clinically divided into FSH- or LH-predominant types according to their preoperative serum FSH/LH ratio. The expressions of related genes in the tumor tissues of female FGAs, non-functioning gonadotroph adenomas (NFGAs), and silent corticotropin adenomas were evaluated by RT-qPCR.

Results: Of all the 12 patients with FGAs from our center, 11 (91.7%) were diagnosed as FSH-predominant type, and they all had menstrual disorders, including 9 with spontaneous ovarian hyperstimulation syndrome (sOHSS). Their hormonal profiles showed non-suppressed FSH (12.45 ± 7.34 IU/L) with hyperestrogenemia [median estradiol level 1353.0 pg/mL (636.0, 3535.0)]. The other patient (8.3%) with LH-predominant type mainly manifested with infertility and sustained elevated serum LH without FSH or estradiol increasing. 65 premenopausal FGAs patients were systematic reviewed. 60 patients (92.3%) were FSH-predominant type, including 86.7% presented with menstrual disorders, 16.7% reported infertility, and 98.2% (55/56) showed sOHSS. No sOHSS or hyperestrogenemia were found in the 5 patients (7.7%) with LH-predominant type. Pituitary imaging data revealed macroadenomas and microadenomas accounted for 89.2% and 10.8%, respectively. Of 63 patients (96.9%) who underwent pituitary adenoma resection, 77.8% had complete tumor resection and no recurrence at the last follow-up. The relative expressions of KISS1 mRNA were significantly higher in FGA group than in NFGA group (p = 0.018), and significantly positively correlated with the preoperative serum estradiol levels (p = 0.004).

Conclusions: Different clinical features were observed in premenopausal women with FGAs of FSH- or LH-predominant types. The elevated KISS1 expression in tumor tissues might involve in the secretion function of FGAs.
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http://dx.doi.org/10.1007/s11102-021-01205-9DOI Listing
June 2022

Pituitary adenoma or pituitary neuroendocrine tumor: a narrative review of controversy and perspective.

Transl Cancer Res 2021 Apr;10(4):1916-1920

Department of Neurosurgery, Xuanwu Hospital Capital Medical University, Beijing, China.

In 1932, Harvey Cushing first proposed pituitary adenoma (PA) as the term for the cause of acromegaly. After nearly 90 years of research, PA is recognized as the second most common intracranial neoplasm. Most PAs can be easily cured or controlled by conventional therapies, including surgery, medical treatment or radiotherapy. However, nearly 40% of PAs are invasive, and some adenomas show aggressive behavior, with rapid growth patterns and resistance to conventional treatments, which leads to a poor prognosis; this type of adenoma is called aggressive or refractory PA. For a very small proportion of PAs (approximately 0.2%), subarachnoid or systemic metastasis may develop, at which point it is considered malignant and called pituitary carcinoma. Based on distinctions regarding the biological behaviors of adenoma, aggressive adenoma and pituitary carcinoma, the International Pituitary Pathology Club in 2016 formally proposed new terminology for PA: pituitary neuroendocrine tumor (PitNET). Over the last three years, an increasing number of relevant articles have used the term PitNET in place of PA. Interestingly, the fourth edition of the WHO classification of PA released in 2017 did not adopt this nomenclature, and the Pituitary Society published a paper in 2019 suggesting that the new nomenclature does not improve clinical diagnosis or treatment and confuses patients more than the PA terminology. The Pituitary Society insists on using the term PA, as PAs with aggressive behavior only account for a very small proportion of all PAs. Overall, the new terminology may cause significant and unnecessary patient anxiety and confusion. Here, we describe the current perspectives and bases of the two naming methods and offer our opinions on maintaining the original naming system for PA. Nevertheless, early diagnosis and intensive treatment of aggressive PAs is extremely important for improving patient prognosis, regardless of the nomenclature.
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http://dx.doi.org/10.21037/tcr-20-3446DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8798339PMC
April 2021

The Patterns of Morphological Change During Intracerebral Hemorrhage Expansion: A Multicenter Retrospective Cohort Study.

Front Med (Lausanne) 2021 13;8:774632. Epub 2022 Jan 13.

Department of Neurosurgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.

Hemorrhage expansion (HE) is a common and serious condition in patients with intracerebral hemorrhage (ICH). In contrast to the volume changes, little is known about the morphological changes that occur during HE. We developed a novel method to explore the patterns of morphological change and investigate the clinical significance of this change in ICH patients. The morphological changes in the hematomas of ICH patients with available paired non-contrast CT data were described in quantitative terms, including the diameters of each hematoma in three dimensions, the longitudinal axis type, the surface regularity (SR) index, the length and direction changes of the diameters, and the distance and direction of movement of the center of the hematoma. The patterns were explored by descriptive analysis and difference analysis in subgroups. We also established a prognostic nomogram model for poor outcomes in ICH patients using both morphological changes and clinical parameters. A total of 1,094 eligible patients from four medical centers met the inclusion criteria. In 266 (24.3%) cases, the hematomas enlarged; the median absolute increase in volume was 14.0 [interquartile range (IQR), 17.9] mL. The initial hematomas tended to have a more irregular shape, reflected by a larger surface regularity index, than the developed hematomas. In subtentorial and deep supratentorial hematomas, the center moved in the direction of gravity. The distance of center movement and the length changes of the diameters were small, with median values of less than 4 mm. The most common longitudinal axis type was anterior-posterior (64.7%), and the axis type did not change between initial and repeat imaging in most patients (95.2%). A prognostic nomogram model including lateral expansion, a parameter of morphological change, showed good performance in predicting poor clinical outcomes in ICH patients. The present study provides a morphological perspective on HE using a novel automatic approach. We identified certain patterns of morphological change in HE, and we believe that some morphological change parameters could help physicians predict the prognosis of ICH patients.
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http://dx.doi.org/10.3389/fmed.2021.774632DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8792842PMC
January 2022

Diagnosis of invasive non-functional pituitary adenomas using exosomal biomarkers.

Clin Chim Acta 2022 Apr 24;529:25-33. Epub 2022 Jan 24.

Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China. Electronic address:

Background And Aims: Incomplete surgical resection of invasive non-functional pituitary adenomas (NFPAs) produces a risk of the subsequent development of complications which will require treatment with powerful drugs and adjuvant radiotherapy.

Materials And Methods: The degree of invasiveness of NFPA can be established using biomarkers to help clinicians choose appropriate treatment for these patients.

Results: This research explored transcriptomic and proteomic variations of non-invasive and invasive NFPAs, other forms of pituitary adenomas and evaluated exosomal genetic markers associated with these diseases. Increased expression of matrix metalloproteinase-1 (MMP1) and its formation in exosomes (exo-MMP1) were correlated with the characteristic invasiveness of NFPAs. Changes in the expression of MMP1 in the exosome was synchronized with transduction of NFPA cells. Enrichment of MMP1 stimulated migration, growth and angiogenesis in tumors through the protease-activated receptor-1 signaling pathway in cells.

Conclusion: The results revealed that MMP1 activity has obligatory actions in promoting tumor invasion and angiogenesis, and that the exosome-mediated regulatory pathway for MMP1 may be a novel therapeutic target.
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http://dx.doi.org/10.1016/j.cca.2022.01.014DOI Listing
April 2022

MicroRNA-30d target TIMP3 induces pituitary tumor cell growth and invasion.

Gland Surg 2021 Dec;10(12):3314-3323

Department of Neurosurgery, Affiliated Beijing Tongren Hospital, Capital Medical University, Beijing, China.

Background: As one of the most common intracranial tumors, pituitary adenomas, especially the Cushing's disease subtype, have been studied for many years. However, at present, effective methods for the early diagnosis of pituitary adenomas are very limited, especially for subtypes such as Cushing's disease. Therefore, it is of urgent importance to find effective molecular targets to develop new diagnostic and therapeutic methods for pituitary adenomas.

Methods: We showed the abnormally high expression of miR-30d in pituitary adenomas by analyzing data in the Gene Expression Omnibus (GEO) database and revealed a novel molecular mechanism of miR-30d in regulating the proliferation and invasion of a pituitary adenoma cell line (AtT-20). Cell culture and transfection, and RNA interference (RNAi) were used to treat AtT-20 cells to test the effects of miR-30d and TIMP3 on cells. Quantitative polymerase chain reaction (qPCR) was used to determine the messenger RNA (mRNA) expressions. We used 3-(4,5-diphenyltetrazolium bromide) (MTT) to determine cell viabilities. An invasion assay was performed using Transwell chambers. Luciferase activity was tested with a dual-luciferase assay.

Results: We found that the expression of miR-30d in pituitary adenoma was higher than that in normal pituitary tissues. It was revealed that miR-30d promoted the proliferation and invasion of AtT-20 cells by inhibiting the expression of TIMP3. In the above process, miR-30d could bind to the 3'-untranslated region (3'-UTR) of TIMP3 mRNA.

Conclusions: The mir-30d/TIMP3 signaling pathway plays an important regulatory role in pituitary adenomas. These new discoveries may reveal more functions of miR-30d and lay the foundation for future clinical development of new drug targets.
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http://dx.doi.org/10.21037/gs-21-720DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8749101PMC
December 2021

The Application of Artificial Intelligence and Machine Learning in Pituitary Adenomas.

Front Oncol 2021 23;11:784819. Epub 2021 Dec 23.

Department of Neurosurgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China.

Pituitary adenomas (PAs) are a group of tumors with complex and heterogeneous clinical manifestations. Early accurate diagnosis, individualized management, and precise prediction of the treatment response and prognosis of patients with PA are urgently needed. Artificial intelligence (AI) and machine learning (ML) have garnered increasing attention to quantitatively analyze complex medical data to improve individualized care for patients with PAs. Therefore, we critically examined the current use of AI and ML in the management of patients with PAs, and we propose improvements for future uses of AI and ML in patients with PAs. AI and ML can automatically extract many quantitative features based on massive medical data; moreover, related diagnosis and prediction models can be developed through quantitative analysis. Previous studies have suggested that AI and ML have wide applications in early accurate diagnosis; individualized treatment; predicting the response to treatments, including surgery, medications, and radiotherapy; and predicting the outcomes of patients with PAs. In addition, facial imaging-based AI and ML, pathological picture-based AI and ML, and surgical microscopic video-based AI and ML have also been reported to be useful in assisting the management of patients with PAs. In conclusion, the current use of AI and ML models has the potential to assist doctors and patients in making crucial surgical decisions by providing an accurate diagnosis, response to treatment, and prognosis of PAs. These AI and ML models can improve the quality and safety of medical services for patients with PAs and reduce the complication rates of neurosurgery. Further work is needed to obtain more reliable algorithms with high accuracy, sensitivity, and specificity for the management of PA patients.
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http://dx.doi.org/10.3389/fonc.2021.784819DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8733587PMC
December 2021

Clinical Characteristics for the Improvement of Cushing's Syndrome Complicated With Cardiomyopathy After Treatment With a Literature Review.

Front Cardiovasc Med 2021 1;8:777964. Epub 2021 Dec 1.

Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.

Endogenous Cushing's syndrome (CS), also called hypercortisolism, leads to a significant increase in mortality due to excessive cortisol production, which is mainly due to cardiovascular disease. CS complicated with cardiomyopathies, which is a rare and severe condition, has rarely been reported in the literature. To investigate the clinical characteristics of CS complicated with cardiomyopathies, we retrospectively reviewed the clinical manifestations, laboratory results, cardiac imaging results and prognosis to further understand the diagnosis, treatment, and management of these cases. The clinical data of patients diagnosed with CS complicated with cardiomyopathies obtained from discharge sheets from Peking Union Medical College Hospital from January 1986 to August 2021 were collected. Case reports of CS complicated with cardiomyopathies were retrieved from PubMed. In addition, Cushing's disease (CD) patients without cardiomyopathies were collected as controls to compare the clinical features. A total of 19 cases of CS complicated with cardiomyopathies and cases of CD without cardiomyopathies ( = 242) were collected. The causes of CS included pituitary adenoma ( = 8, 42.11%), adrenal adenoma ( = 7, 36.84%), ectopic adrenocorticotropic hormone (ACTH) tumor ( = 2, 10.53%) and unclear causes ( = 2, 10.53%) in the CS complicated with cardiomyopathies group. The types of cardiomyopathies were dilated cardiomyopathies ( = 15, 78.94%) and hypertrophic cardiomyopathies ( = 4, 21.05%). The serum sodium concentration was significantly higher [145.50 (140.50-148.00) mmol/L vs. 141.00 (140.00-143.00) mmol/L], while the serum potassium concentration was significantly lower [2.70 (2.40-3.60) mmol/L] vs. 3.90 (3.50-4.20 mmol/L)] in the CS complicated with cardiomyopathies group compared to the CD patients without cardiomyopathies. There were no significant differences between the CS complicated with cardiomyopathies group and the CD patients without cardiomyopathies in the serum cortisol concentration and 24-h urine free cortisol, but a significant difference in the adrenocorticotropic hormone level [109.00 (91.78-170.30) pg/ml vs. 68.60 (47.85-110.00) pg/ml]. Twelve/16 (75.0%) patients showed significant improvement or even a complete healing of the heart structure and function after remission of hypercortisolemia after treatment with CS. CS complicated with cardiomyopathies is a very rare clinical entity, in which cortisol plays an important role and it can be greatly improved after remission of hypercortisolemia.
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http://dx.doi.org/10.3389/fcvm.2021.777964DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8671741PMC
December 2021

An Update on Silent Corticotroph Adenomas: Diagnosis, Mechanisms, Clinical Features, and Management.

Cancers (Basel) 2021 Dec 6;13(23). Epub 2021 Dec 6.

Pituitary Center, Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730, China.

With the introduction of 2017 World Health Organization (WHO) classification of endocrine tumors, T-PIT can serve as a complementary tool for identification of silent corticotroph adenomas (SCAs) in some cases if the tumor is not classifiable by pituitary hormone expression in pathological tissue samples. An increase of the proportion of SCAs among the non-functioning pituitary adenomas (NFPAs) has been witnessed under the new rule with the detection of T-PIT-positive ACTH-negative SCAs. Studies of molecular mechanisms related to SCA pathogenesis will provide new directions for the diagnosis and management of SCAs. A precise pathological diagnosis can help clinicians better identify SCAs. Understanding clinical features in the context of the pathophysiology of SCAs is critical for optimal management. It could provide information on appropriate follow-up time and aid in early recognition and treatment of potentially aggressive forms. Management approaches include surgical, radiation, and/or medical therapies.
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http://dx.doi.org/10.3390/cancers13236134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8656508PMC
December 2021

Neuroimaging Features of Optic Nerve Hemangioblastoma Identified by Conventional and Advanced Magnetic Resonance Techniques: A Case Report and Literature Review.

Front Oncol 2021 12;11:763696. Epub 2021 Nov 12.

Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Optic nerve hemangioblastoma is a very rare benign tumor with only 39 reported cases by now. It appears to be hyperintense on T2-weighted images with a significant enhancement on contrast scans, which are similar to glioma and meningioma. Due to the lack of specificity in MRI manifestations, optic nerve hemangioblastoma is often misdiagnosed. To provide new insights into differential diagnosis of optic nerve hemangioblastoma, we report for the first time an optic nerve hemangioblastoma case employing advanced magnetic resonance techniques including diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC) maps, and magnetic resonance angiography (MRA). In addition, we have collected all reported optic nerve hemangioblastoma cases and reviewed their neuroimaging findings by MRI and angiography. Our results show that solid-type tumor is the dominant form of optic nerve hemangioblastoma and extensive edema is widely observed. These findings are surprisingly contrary to manifestations of cerebellar hemangioblastoma. Besides the structural features, quantitative indexes including ADC and relative cerebral blood volume (rCBV) ratio, which are significantly elevated in cerebellar hemangioblastoma, may also shed a light on the preoperative diagnosis of hemangioblastoma of optic nerve. Finally, we discuss the critical neuroimaging features in the differential diagnosis between optic nerve hemangioblastoma from optic pathway glioma and optic nerve sheath meningioma.
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http://dx.doi.org/10.3389/fonc.2021.763696DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8632699PMC
November 2021

Diagnosis, Manifestations, Laboratory Investigations, and Prognosis in Pediatric and Adult Cushing's Disease in a Large Center in China.

Front Endocrinol (Lausanne) 2021 19;12:749246. Epub 2021 Nov 19.

Department of Neurosurgery, Pituitary Centre, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.

Purpose: Cushing's disease (CD) is a rare disease that contributes to 70-80% hypercortisolemia, which presents similarities and differences between pediatric and adult patients, and even between male and female patients. However, the comparative study of CD between different age groups and different genders is still insufficient. The aim of the study is to make a systematic comparison to reveal the gender differences in children and adult patients of CD, helping clinicians to provide optimal treatment for different groups of patients.

Methods: We conducted a retrospective research consisting of 30 pediatric and 392 adult CD patients in a single center in Peking Union Medical College Hospital. All 422 patients showed symptoms related to hypercortisolism and received adenoma excision surgery in the department of neurosurgery between 2014 and 2020.

Results: For the accuracy of diagnosis, the sensitivity of BIPSS at baseline in pediatric patients was lower than in adults (75 91%, P = 0.054) but increased greatly after desmopressin stimulation (94 95%). However, the accuracy of lateralization for BIPSS was not preferred for prediction. As for clinical manifestations, growth retardation, weight gain, hirsutism, and acne were more prevalent for children, while for adults, hypertension, osteopenia, glucometabolic disorder, easy bruising, hair loss, and weight loss were more frequently seen. As previously reported, we observed a significant difference between the male prevalence of pediatric and adult patients (50 17%, P < 0.001), which was possibly caused by the more severe and earlier onset of a series of symptoms. Gender-related comparison showed greater morbidity of nephrolithiasis, hypokalemia, hypertension, easy bruising, osteopenia, and striae for male patients, while irregular menses, hirsutism, and hair loss were more common for female patients. Further analysis showed that the secretory activity of the PA axis was higher for males, presenting as the more remarkable alteration of laboratory parameters and contributing to the more severe clinical manifestations. For patients treated with transsphenoidal pituitary surgery (TSS), the immediate prognosis could be predicted by operation history, invasiveness, Ki-67, and information provided by MRI, including tumor size and Knosp grading. However, we still lack methods to predict long-term prognosis.

Conclusions: Our study is the first detailed and systematic comparison between pediatric and adult CD patients. Further exploration of the impact of CD on different genders reveals a more severe and probably an earlier-onset pattern of CD for male patients.
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http://dx.doi.org/10.3389/fendo.2021.749246DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8640923PMC
February 2022

Basal Ganglia Germ Cell Tumors With or Without Sellar Involvement: A Long-Term Follow-Up in a Single Medical Center and a Systematic Literature Review.

Front Endocrinol (Lausanne) 2021 10;12:763609. Epub 2021 Nov 10.

Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.

Background: Basal ganglia germ cell tumors (BGGCTs) represent an extremely rare subset of tumors about which little is known. Some patients suffer from tumor dissemination, such as sellar involvement. This study aimed to evaluate the independent prognostic risk factors of patients with BGGCTs with or without sellar involvement.

Methods: Sixteen patients were diagnosed with BGGCTs at Peking Union Medical College Hospital from January 2000 to December 2020. A literature review was performed on the online databases Medline and PubMed, and 76 cases in the 19 retrieved articles were identified at the same time. The data regarding biochemical tests, radiological examinations, and outcomes during follow-up were analyzed.

Results: Of 92 patients in this study, seven patients were clinically diagnosed as germinomas, with the remaining 85 patients receiving surgery. Fifty-two patients suffered from multifocal lesions or tumor dissemination. The patients with BGGCTs demonstrated a significant male predilection. The patients with delayed diagnosis more likely had cognitive disturbance (p = 0.028), mental disturbance (p = 0.047), and diabetes insipidus (p = 0.02). Multivariate analysis demonstrated that the independent poor prognostic risk factors of patients with BGGCTs were delayed diagnosis [odd ratio (OR) 2.33; 95% CI 1.02-5.31], focal radiotherapy (OR 4.00; 95% CI 1.69-9.49), and non-pure germinoma (OR 4.64; 95% CI 1.76-12.22).

Conclusions: The delayed diagnosis, focal radiotherapy, and non-pure germinoma were associated with a poorer prognosis for patients with BGGCTs with or without sellar involvement.
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http://dx.doi.org/10.3389/fendo.2021.763609DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8631754PMC
February 2022

Clinical Characteristics and Management of Patients With McCune-Albright Syndrome With GH Excess and Precocious Puberty: A Case Series and Literature Review.

Front Endocrinol (Lausanne) 2021 29;12:672394. Epub 2021 Oct 29.

Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, State Key Laboratory of Complex Severe and Rare Diseases Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.

Background: McCune-Albright syndrome is a rare disorder characterized by fibrous dysplasia, café au lait skin spots, and hyperfunctioning endocrinopathies. The coexistence of precocious puberty and growth hormone excess in McCune-Albright syndrome is rare. Both conditions can manifest as accelerated growth, and treatments can be more challenging for such patients. This study aimed to describe the clinical manifestations of combined GH excess and PP in the context of McCune-Albright syndrome and analyze the clinical features and treatments of these patients.

Method: Clinical data from 60 McCune-Albright syndrome patients from Peking Union Medical College Hospital were obtained. The demographic characteristics, growth hormone, insulin-like growth factor-1, prolactin, alkaline phosphatase, and sex hormone levels; growth velocity; and bone age data were obtained. The growth velocity Z-score, bone age over chronological age ratio, and predicted adult height Z-score were calculated before and after treatment. Published studies and case reports were systemically searched, and data on demographic, clinical, and biochemical characteristics and treatment outcomes were obtained.

Results: We reviewed seven patients among 60 McCune-Albright syndrome patients at Peking Union Medical College Hospital (5 female) and 39 patients (25 female) from the published literature. Six of the seven patients from Peking Union Medical College Hospital and half of the patients from the published studies were pediatric patients. These patients had increased growth velocity Z-scores and bone age over chronological age ratios. After good control of both conditions, the growth velocity Z-score and bone age over chronological age ratio decreased significantly, and the predicted adult height Z-score increased. The final heights and predicted adult height Z-scores were not impaired in patients with gigantism. All the patients had craniofacial fibrous dysplasia associated with optic and otologic complications.

Conclusion: McCune-Albright syndrome with growth hormone excess and precocious puberty is more common in girls. Patients have accelerated linear growth and advanced skeletal age, and early and good control of both conditions leads to a reduced growth velocity and stabilized bone age. The predicted adult and final heights are not negatively affected when growth hormone excess is diagnosed in pediatric patients.
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http://dx.doi.org/10.3389/fendo.2021.672394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8586495PMC
December 2021

Perihematomal Edema After Intracerebral Hemorrhage: An Update on Pathogenesis, Risk Factors, and Therapeutic Advances.

Front Immunol 2021 19;12:740632. Epub 2021 Oct 19.

Department of Neurosurgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.

Intracerebral hemorrhage (ICH) has one of the worst prognoses among patients with stroke. Surgical measures have been adopted to relieve the mass effect of the hematoma, and developing targeted therapy against secondary brain injury (SBI) after ICH is equally essential. Numerous preclinical and clinical studies have demonstrated that perihematomal edema (PHE) is a quantifiable marker of SBI after ICH and is associated with a poor prognosis. Thus, PHE has been considered a promising therapeutic target for ICH. However, the findings derived from existing studies on PHE are disparate and unclear. Therefore, it is necessary to classify, compare, and summarize the existing studies on PHE. In this review, we describe the growth characteristics and relevant underlying mechanism of PHE, analyze the contributions of different risk factors to PHE, present the potential impact of PHE on patient outcomes, and discuss the currently available therapeutic strategies.
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http://dx.doi.org/10.3389/fimmu.2021.740632DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8560684PMC
January 2022

Electronic Medical Records as Input to Predict Postoperative Immediate Remission of Cushing's Disease: Application of Word Embedding.

Front Oncol 2021 13;11:754882. Epub 2021 Oct 13.

Department of Neurosurgery, Chinese Academy of Medical Sciences and Peking Union Medical College, Peking Union Medical College Hospital, Beijing, China.

Background: No existing machine learning (ML)-based models use free text from electronic medical records (EMR) as input to predict immediate remission (IR) of Cushing's disease (CD) after transsphenoidal surgery.

Purpose: The aim of the present study is to develop an ML-based model that uses EMR that include both structured features and free text as input to preoperatively predict IR after transsphenoidal surgery.

Methods: A total of 419 patients with CD from Peking Union Medical College Hospital were enrolled between January 2014 and August 2020. The EMR of the patients were embedded and transformed into low-dimensional dense vectors that can be included in four ML-based models together with structured features. The area under the curve (AUC) of receiver operating characteristic curves was used to evaluate the performance of the models.

Results: The overall remission rate of the 419 patients was 75.7%. From the results of logistic multivariate analysis, operation ( < 0.001), invasion of cavernous sinus from MRI ( = 0.046), and ACTH ( = 0.024) were strongly correlated with IR. The AUC values for the four ML-based models ranged from 0.686 to 0.793. The highest AUC value (0.793) was for logistic regression when 11 structured features and "individual conclusions of the case by doctor" were included.

Conclusion: An ML-based model was developed using both structured and unstructured features (after being processed using a word embedding method) as input to preoperatively predict postoperative IR.
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http://dx.doi.org/10.3389/fonc.2021.754882DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8548651PMC
October 2021

Machine-Learning Prediction of Postoperative Pituitary Hormonal Outcomes in Nonfunctioning Pituitary Adenomas: A Multicenter Study.

Front Endocrinol (Lausanne) 2021 7;12:748725. Epub 2021 Oct 7.

Department of Neurosurgery, The Fuzong Clinical Medical College of Fujian Medical University, Fuzhou, China.

Objective: No accurate predictive models were identified for hormonal prognosis in non-functioning pituitary adenoma (NFPA). This study aimed to develop machine learning (ML) models to facilitate the prognostic assessment of pituitary hormonal outcomes after surgery.

Methods: A total of 215 male patients with NFPA, who underwent surgery in four medical centers from 2015 to 2021, were retrospectively reviewed. The data were pooled after heterogeneity assessment, and they were randomly divided into training and testing sets (172:43). Six ML models and logistic regression models were developed using six anterior pituitary hormones.

Results: Only thyroid-stimulating hormone ( < 0.001), follicle-stimulating hormone ( < 0.001), and prolactin (PRL; < 0.001) decreased significantly following surgery, whereas growth hormone (GH) ( < 0.001) increased significantly. The postoperative GH ( = 0.07) levels were slightly higher in patients with gross total resection, but the PRL ( = 0.03) level was significantly lower than that in patients with subtotal resection. The optimal model achieved area-under-the-receiver-operating-characteristic-curve values of 0.82, 0.74, and 0.85 in predicting hormonal hypofunction, new deficiency, and hormonal recovery following surgery, respectively. According to feature importance analyses, the preoperative levels of the same type and other hormones were all important in predicting postoperative individual hormonal hypofunction.

Conclusion: Fluctuation in anterior pituitary hormones varies with increases and decreases because of transsphenoidal surgery. The ML models could accurately predict postoperative pituitary outcomes based on preoperative anterior pituitary hormones in NFPA.
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http://dx.doi.org/10.3389/fendo.2021.748725DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8529112PMC
February 2022

Suprasellar Mature Cystic Teratoma Mimicking Rathke's Cleft Cyst: A Case Report and Systematic Review of the Literature.

Front Endocrinol (Lausanne) 2021 30;12:731088. Epub 2021 Sep 30.

Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

In this article, we present a 31-year-old female who presented with intermittent headache and oligomenorrhea of over 10 years' duration. Imaging revealed a large suprasellar mass with sellar extension. The patient underwent an endoscopic endonasal trans-sphenoidal surgery to resection of the mass. Clinical, radiological, and operative findings from this patient were initially considered to be Rathke's cleft cyst (RCC). However, postoperative histological examinations revealed a mature cystic teratoma. No radiotherapy was performed after surgery. At the most recent follow-up, approximately 1 year later, the patient is doing well with no headache and no recurrence of the teratoma.
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http://dx.doi.org/10.3389/fendo.2021.731088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8515142PMC
February 2022

Weakly supervised multitask learning models to identify symptom onset time of unclear-onset intracerebral hemorrhage.

Int J Stroke 2022 Aug 17;17(7):785-792. Epub 2021 Oct 17.

Neurosurgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.

Background: Approximately one-third of spontaneous intracerebral hemorrhage patients did not know the onset time and were excluded from studies about time-dependent treatments for hyperacute spontaneous intracerebral hemorrhage.

Aims: To help clinicians explore the benefit of time-dependent treatments for unclear-onset patients, we presented artificial intelligence models to identify onset time using non-contrast computed tomography (NCCT) based on weakly supervised multitask learning (WS-MTL) structure.

Methods: The patients with reliable symptom onset time (strong label) or repeat CT (weak label) were included and split into training set and test set (internal and external). The WS-MTL structure utilized strong and weak labels simultaneously to improve performance. The models included three binary classification models for classifying whether NCCT acquired within 6, 8 or 12 h for different treatments measured by area under curve, and a regression model for determining the exact onset time measured by mean absolute error. The generalizability of models was also explored in comprehensive analysis.

Results: A total of 4004 patients with 10,780 NCCT scans were included. The performance of WS-MTL classification model showed high accuracy, and that of regression model was satisfactory in ≤6 h subgroup. In comprehensive analysis, the WS-MTL showed better performance for larger hematomas and thinner scans. And the performance improved effectively as training amounts increasing and could be improved steadily through retraining.

Conclusions: The WS-MTL models showed good performance and generalizability. Considering the large number of unclear-onset spontaneous intracerebral hemorrhage patients, it may be worth to integrate the WS-MTL model into clinical practice to identify the onset time.
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http://dx.doi.org/10.1177/17474930211051531DOI Listing
August 2022
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